Search PubMed⌕ Search

Biomedical subjects

J M Bruner

Publications and source records attributed to J M Bruner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Sulfonylurea receptor mRNA expression in pituitary macroadenomas.

ATP-sensitive K+ (KATP) channels modulated by sulfonylurea compounds have been previously identified in the anterior pituitary of the rat and have been demonstrated to influence GH release. Recently, a sulfonylurea receptor (SUR) has been cloned from an islet cell tumor and identified as a member of the ATP binding cassette superfamily capable to coupling with inwardly rectifying potassium channels. To determine if the same receptor is expressed in pituitary tumors, SUR mRNA levels were measured in 28 human macroadenoma specimens using an RNase protection assay. All immunonegative, corticotrophin (ACTH), growth hormone (GH), and GH/prolactin (GH/Prl) immunostaining tumors expressed detectable amounts of SUR message. Among these tumors, only the GH and GH/ Prl adenomas were functional. Of the tumors immunostaining for luteinizing hormone (LH), follicle-stimulating hormone (FSH), or both, SUR mRNA was present in small amounts in 5/11. Only 1/3 Prl immunostaining tumors contained SUR mRNA. In summary, we have demonstrated that SUR mRNA expression is common in several types of silent pituitary adenomas and in functional tumors that secrete GH. Lower levels are seen in some gonadotrophin immunostaining tumors.

ATP-Binding Cassette Transporters↗
PubMed1998

The descriptive epidemiology of craniopharyngioma.

OBJECT: In this report the authors describe the epidemiology of craniopharyngioma. METHODS: The incidence of craniopharyngioma in the United States was estimated from two population-based cancer registries that include brain tumors of benign and borderline malignancy: the Central Brain Tumor Registry of the United States (CBTRUS) and the Los Angeles county Cancer Surveillance Program. Information on additional pediatric tumors was available from the Greater Delaware Valley Pediatric Tumor Registry (GDVPTR). The overall incidence of craniopharyngioma was 0.13 per 100,000 person years and did not vary by gender or race. A bimodal distribution by age was noted with peak incidence rates in children (aged 5-14 years) and among older adults (aged 65-74 years in CBTRUS and 50-74 years in Los Angeles county). Survival information was available from GDVPTR and the National Cancer Data Base (NCDB), a hospital-based reporting system. In the NCDB, the 5-year survival rate was 80% and decreased with older age at diagnosis. Survival is higher among children and has improved in recent years. CONCLUSIONS: Craniopharyngioma is a rare brain tumor of uncertain behavior that occurs at a rate of 1.3 per million person years. Approximately 338 cases of this disease are expected to occur annually in the United States, with 96 occurring in children from 0 to 14 years of age.

Adolescent↗
PubMed1998

Genetic polymorphisms in glutathione S-transferase mu and theta, N-acetyltransferase, and CYP1A1 and risk of gliomas.

The role of genetic polymorphisms in modulating susceptibility to carcinogenic exposures has been well explored for tobacco-related neoplasms but not for other neoplasms including gliomas. It is relevant to explore these polymorphisms because certain carcinogenic exposures such as nitrosamines are implicated in the risk of gliomas. We therefore conducted a pilot case-control study to examine the role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with glioma were ascertained as part of an ongoing genetic epidemiological study and were age, gender, and race matched with 90 healthy controls. We used PCR based methodology to determine the prevalence of the above genetic polymorphisms using sequences and PCR conditions directly adapted from studies reported previously. We calculated univariate odds ratios and performed multiple logistic regression to assess interactions between polymorphisms. We found no statistically significant associations between the null genotypes of GSTM1 and GSTT1, and CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2 acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate, and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any single polymorphism is sufficiently predictive of risk, and a panel of markers integrated with epidemiological data should be conducted on a large number of study subjects to fully understand the role of genetic polymorphisms and brain tumor risk.

Adult↗
PubMed1997

The descriptive epidemiology of craniopharyngioma.

The incidence of craniopharyngioma in the United States was estimated from two population-based cancer registries that include brain tumors of benign and borderline malignancy: the Central Brain Tumor Registry of the United States (CBTRUS) and Los Angeles county. Information on additional pediatric tumors was available from the Greater Delaware Valley Pediatric Tumor Registry (GDVPTR). The overall incidence of craniopharyngioma was 0.13 per 100,000 person years and did not vary by gender or race. A bimodal distribution by age was noted with peak incidence rates in children (aged 5-14 years) and among older adults (aged 65-74 years in CBTRUS and 50-74 years in Los Angeles county). Survival information was available from GDVPTR and the National Cancer Data Base (NCDB), a hospital-based reporting system. In the NCDB, the 5-year survival rate was 80% and decreased with older age at diagnosis. Survival is higher among children and has improved in recent years. Approximately 338 cases of craniopharyngiomas are expected to occur annually in the United States, with 96 occurring in children from 0 to 14 years of age.

Journal Article↗
PubMed1997

High feline trypsin-like immunoreactivity in a cat with pancreatitis and hepatic lipidosis.

A 1.5-year-old domestic shorthair cat was examined because of vomiting and icterus. Clinicopathologic abnormalities included high alanine transaminase, alkaline phosphatase, and gamma-glutamyltransferase activities and high total bilirubin concentration. During abdominal ultrasonography, the left limb and body of the pancreas appeared hypoechoic, and a small quantity of peritoneal effusion was seen. The liver was diffusely hyperechoic, with echogenicity similar to that of the spleen, indicating hepatic lipidosis. Feline trypsin-like immunoreactivity was high, suggesting that the cat also had pancreatitis. The cat was treated with crystalloid fluids and was fed a protein-restricted diet via a percutaneous endoscopically placed gastrostomy tube. The cat's condition continued to deteriorate despite medical treatment, and it was euthanatized. Necropsy confirmed the clinical suspicion of acute pancreatitis and hepatic lipidosis. This case suggests that measurement of trypsin-like immunoreactivity may be useful in cats suspected of having pancreatitis.

Alanine Transaminase↗
PubMed1997

Reduced expression of mismatch repair genes measured by multiplex reverse transcription-polymerase chain reaction in human gliomas.

Microsatellite instability (MIN) is frequently observed in hereditary nonpolyposis colon cancer and in other sporadic cancers including gliomas. Abnormalities in at least one of five mismatch repair (MMR) genes are implicated in the development of cancers in hereditary nonpolyposis colon cancer and the associated MIN. Using a newly developed multiplex reverse transcription-PCR assay, we evaluated the expression of the five known human MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and GTBP) in human gliomas by measuring simultaneously the relative levels of the transcripts. The beta-actin gene was used as an internal control for RNA degradation and DNA contamination and as a reference for quantifying the levels of their transcripts. Of the 33 gliomas examined, 42% (14) had low expression of hMSH2 (at least 4-5-fold lower than normal mean), 21% (7) had low expression of hMLH1, and 18% (6) had low expression of hPMS1 compared with the expression in the lymphocytes from 13 normal individuals. Furthermore, six of the 33 (18%) tumor samples had decreased expression of more than one MMR gene. Two of these six patients with multiple gene abnormalities had second primary cancers, and an additional patient had multifocal gliomas. Further molecular analysis of available DNA samples indicated that one of five of those tumors with aberrant expression of MMR genes had MIN, as compared with none of five tumors with normal expression. These data suggest that reduced expression of MMR genes is frequent in human gliomas and that aberrant expression of more than one MMR gene may be associated with increased risk of second primary malignancies in glioma patients.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Diagnostic discrepancies and their clinical impact in a neuropathology referral practice.

BACKGROUND: During the course of their neuropathology practice, the authors received cases to review in consultation. In some cases, the patients came to the authors' hospital for therapy; in others, the primary pathologists requested a consultation. Because changes in diagnosis might significantly alter patient management, protocol entry, care costs, or the potential for physician liability, the authors determined the frequency and degrees of their disagreements with the original diagnoses submitted to them. METHODS: The authors reviewed the first 500 brain or spinal cord biopsy cases that were submitted to their neuropathology consultation service for a second opinion in 1995. Disagreements were coded into 10 categories, but were grouped for this analysis as follows: serious (having immediate significance for therapy or intervention), less serious but potentially substantial (calling for a change in type or grade of glioma), minor (adding or deleting information), and those in which the authors made the first diagnosis themselves. RESULTS: There was some degree of disagreement between the original and review diagnoses in 214 (42.8%) of the 500 cases. Disagreements were counted as serious in 44 cases (8.8%), less serious but substantial in 96 cases (19.2%), and minor in 50 cases (10.0%); the authors made the first diagnosis in 24 cases (4.8%). CONCLUSIONS: Clinically important diagnostic errors that can affect immediate patient care decisions occur in a substantial number of brain and spinal cord biopsy cases. Thus, seeking expert neuropathology consultation is prudent and cost-effective for pathologists who are less experienced with these types of cases. Cost savings in case management might result from confirmation of diagnosis before definitive therapy is administered to the patients. The rates of discrepancy between original diagnoses and second opinions in other subspecialties of pathology should be examined.

Biopsy↗
PubMed1997

p53 protein in pediatric malignant astrocytomas: a study of 21 patients.

Malignant astrocytomas are uncommon brain tumors in children and it is known that astrocytic tumors with similar degrees of histologic anaplasia often show different biologic behaviour. Their uncommon occurrence has resulted in relatively few studies of the molecular biology and genetics of pediatric malignant astrocytomas with somewhat conflicting results, in contrast with the many studies addressing astrocytomas in adults. p53 immunoreactivity has been used to screen tissues for the abnormal presence of the p53 protein and abnormal immunoreactivity has been demonstrated in one-half to two-thirds of adult astrocytomas. We studied the frequency of p53 immunoreactivity and gene alteration in 21 children with malignant astrocytomas (anaplastic astrocytoma and glioblastoma multiforme) and analysed the survival of patients with p53 immunoreactive versus non-reactive tumors. Of the cases examined, 8 were anaplastic astrocytoma (AA) and 13 were glioblastoma multiforme (GM). We found that the overall frequency of p53 immunoreactivity of 47% in this group of pediatric malignant astrocytomas is similar to that reported for adult astrocytomas. The median survival in both p53-positive and p53-negative groups of pediatric malignant astrocytomas was similar: however, the number of deaths in each group and the distribution of p53 scores is not statistically significant. Further studies to precisely identify p53 and other genetic mutations in pediatric gliomas are needed to understand their biology and the rationale for therapeutic options.

Adolescent↗
PubMed1997

The treatment of recurrent unresectable and malignant meningiomas with interferon alpha-2B.

OBJECTIVE: Recurrent malignant meningiomas and unresectable meningiomas represent a great therapeutic challenge after the failure of radiation therapy. No effective chemotherapy has been found. We report the preliminary results of the treatment of patients with recurrent unresectable or malignant meningiomas with recombinant interferon alpha-2B (IFN-alpha-2B). METHOD: Each of six patients with either a recurrent malignant meningioma or an unresectable meningioma was treated with IFN-alpha, administered subcutaneously at a dosage of 4 mU/m2 per day, 5 days per week. Two of the six meningiomas were regular, one was atypical, and three were malignant. RESULTS: Five of six patients exhibited positive response to treatment; with stabilization of the size of the tumor in four patients and slight regression in one. The responses observed lasted from 6 to 14 months. The toxicity associated with prolonged use of IFN-alpha was mild and well tolerated. CONCLUSION: These results suggest that IFN-alpha is effective in the treatment of recurrent malignant meningiomas.

Adult↗
PubMed1997

The rationale for standardized registration and reporting of brain and central nervous system tumors in population-based cancer registries.

Most population-based statistical reports of brain and central nervous system (CNS) tumors are limited to data of primary malignant tumors and to summary estimates of all tumor locations and histologies. We argue that data of benign brain and CNS tumors should also be included in registry reports and that standard definitions for the reporting of all brain and CNS tumors by site and histology should exist. We demonstrate current inconsistencies in the definitions of brain and CNS tumor sites used in reports. Grouping of brain and CNS tumors by subtype--which integrates the current World Health Organization classification scheme with the International Classification of Diseases for Oncology coding system used in cancer registries--is proposed. Adoption of standard tumor site and behavior codes for annual reports would aid the comparison of rates of brain and CNS tumors between geographic regions, allow for the evaluation of trends over time, and provide new estimates of tumor subtypes in a more clinically relevant format. A consensus among cancer registries and neuroscientists is needed to adopt standard definitions so that accurate and clinically relevant brain and CNS tumor data are available.

Behavior↗
PubMed1996

Hypermethylation of the CpG island of p16/CDKN2 correlates with gene inactivation in gliomas.

There is considerable evidence that lack of p16 protein expression is a frequent event in human gliomas. Nevertheless, the molecular mechanisms underlying this absence of p16 protein expression are not completely understood. In some gliomas, homozygous deletions are the main cause of p16/CDKN2 gene inactivation. However, other gliomas lacking p16 expression exhibit intact p16/CDKN2 gene, suggesting that p16/CDKN2 is down-regulated at the transcriptional level. In this study we investigated whether aberrant p16/CDKN2 gene methylation correlated with absence of p16 expression in the latter group of gliomas. In a series of 27 gliomas, 12 malignant tumors exhibited loss of p16/CDKN2 expression but not gene deletion. Methylation analysis of the CpG island in the 5' region of the p16/CDKN2 gene showed that exon 1 was extensively methylated in six and partially methylated in the other six of the 12 malignant gliomas. In contrast, no methylation was observed in four other malignant gliomas and two low-grade gliomas that expressed p16 protein. These results indicate that abnormal hypermethylation of the CpG island encompassing the 5' end of the p16/CDKN2 gene may be a mechanism of transcriptional silencing in gliomas without homozygous deletions.

Brain Neoplasms↗
PubMed1996

Mutagen sensitivity and risk of gliomas: a case-control analysis.

Although the risk factors contributing to the etiology of brain tumors remain largely unknown, this pilot study suggests that genetically determined sensitivity to environmental carcinogens may play a role in the pathogenesis of these tumors. In this study, we examined short-term lymphocyte cultures from 45 adult malignant glioma patients and 117 age-, sex-, and ethnicity-matched healthy controls for mutagen-induced chromatid breaks and evaluated their family history of cancer, smoking, and demographic variables to ascertain the association between mutagen sensitivity and risk of brain tumors. The mutagen selected was gamma-radiation. The mean number of induced breaks/cell was 0.72 (SD=0.45) for the cases and 0.45 (SD = 0.35) for the controls (P < 0.0001). Using the median number of induced breaks/cell in the controls as the breakpoint for defining mutagen sensitivity, we observed an unadjusted odds ratio of 5.36 (95% confidence interval = 2.12-13.69) for mutagen sensitivity and brain tumor risk and an adjusted odds ratio of 5.79 (2.26-14.83), when we controlled for epidemiological risk factors including smoking, race, income, and education. Although a larger study is needed to confirm this intriguing result, these preliminary findings suggest that increased sensitivity to radiation is an independent risk factor for gliomas.

Adult↗
PubMed1996

Correlation of p53 immunoreactivity and sequencing in patients with glioma.

This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 cDNA from these samples was analyzed by direct sequencing. Four grades of p53 immunostaining were evaluated: grade 0 = no labeling, grade 1 = less than 5% labeled cells, grade 2 = 5-30% labeled cells, and grade 3 = more than 30% labeled cells. Twenty-six of 36 glioblastomas, 14 of 23 anaplastic gliomas, and none of two low-grade gliomas had positive p53 immunoreactivity. Direct sequencing of PCR-amplified p53 cDNA revealed that 10 glioblastomas, 11 anaplastic gliomas, and no low-grade gliomas had mutations. Comparison of p53 immunostaining and sequencing data revealed that among all the gliomas, mutations were found in three of 21 with p53 grade 0, one of 16 with p53 grade 1, seven of nine with p53 grade 2, and 10 of 15 with p53 grade 3. These results indicate a good correlation between the p53 immunostaining and sequencing data when the percentage of abnormal cells within the tumor was greater than 5% (p53 grades 2 and 3). However, the correlation was poor when the percentage of abnormal cells was less than 5% (p53 grade 1) because of the limited sensitivity of sequencing techniques. Thus, p53 immunostaining may be more accurate in detecting p53 alterations when the percentage of abnormal cells is small; however, in rare cases, p53 immunostaining may fail to detect mutations confirmed by sequencing.

Adult↗
PubMed1996

Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas.

Increasing evidence suggests the existence of polarized human T cell responses described as Th1-type (promoting cell-mediated immunity) and Th2-type (promoting humoral immunity), characterized by a dominant production of either interferon-gamma (IFN-gamma) or IL-4, respectively. Little is known about the intratumoural activation of infiltrating lymphocytes (TIL) in human gliomas. Therefore, we assessed fresh TIL at cellular and molecular levels to find out if they were activated and polarized into a type 1 or 2 immune response. Flow cytometry analysis of TIL revealed that the major subset was made of T lymphocytes. Double labelling with alpha-CD3 and adhesion/ activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, some of which were almost absent in autologous T peripheral blood lymphocytes (T-PBL). Furthermore, the proportions of T-TIL expressing CD56, CD65, or CD25 were several-fold higher than in T-PBL. Intratumoural functional activation of TIL was tested by semiquantitative assessment in relative units (RU) of lymphokine gene activation with mRNA reverse transcriptase-polymerase chain reaction (RT-PCR). All TIL populations except one significantly expressed IL-4 1 to 2 logs of RU above healthy PBL baseline. Similarly, all patients expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) in a range comparable to IL-4. However, most TIL populations did not express IFN-gamma, IL-2, and tumour necrosis factor-beta (TNF-beta) at higher levels than healthy normal PBL. The increase proportion of T cells expressing activation markers and the consistent detection of significant IL-4 and GM-CSF lymphokine gene activation in TIL populations suggested a predominant type 2 intratumoural immune response that does not promote cell-mediated tumouricidal activity and may contribute to the inefficiency of the antiglioma immune response.

Genes, Immunoglobulin↗
PubMed1996

Cytomegalovirus pneumonia in adult nontransplantation patients with cancer: review of 20 cases occurring from 1964 through 1990.

The objectives of this study were to estimate the frequency of cytomegalovirus (CMV) pneumonia and describe its clinical and radiological presentation in adult nontransplantation patients with cancer. Of the 10,441 autopsies performed at M. D. Anderson Cancer Center (Houston) during the period of January 1964 through December 1990, 9,029 were evaluable. Twenty histopathologically confirmed cases of CMV pneumonia were found, representing a frequency of 2.2 cases per 1,000 autopsies. When the frequency of CMV pneumonia was compared for the periods 1964-1979 (1.5 cases per 1,000 autopsies) and 1980-1990 (4.6 cases per 1,000 autopsies), a statistically significant increase due to an increase in the number of patients with solid malignancies was observed (P < .05). CMV pneumonia is an uncommon diagnosis at autopsy for adult nontransplantation patients with cancer and is usually found in conjunction with a disseminated neoplastic process.

Adult↗
PubMed1996

[Expression of fibroblast growth factor receptors (FGFRs) mRNA in human astrocytomas].

Although fibroblast growth factor receptor (FGFR) 4 has been reported not to be expressed in normal human astrocytes, we have demonstrated expression of FGFR-1, -3, and -4 in six human glioblastoma cell lines (SNB19, T98G, UW18, D54 MG, U251MG, and U373MG) by RT-PCR Southern blot analysis. All six lines exhibited predominantly beta-type (with only two extracellular Ig-like domains) FGFR-1 expression. In contrast, FGFR-2 expression was only detected in the UW18 cell line. This evidence support our previous observation that malignant progression in astrocytomas is associated with a shift in FGFR-1 mRNA splicing from the alpha-type (with three extracellular Ig-like domains) to the beta-type with concomitant loss of FGFR-2 expression. It also demonstrates the unique finding that FGFR-4 induction in astrocytomas is associated with transformation. In addition to these cell lines, expression of FGFRs was analyzed in normal human brain tissue and in human astrocytoma tissue samples corresponding to different grades of malignancy. FGFR-4 mRNA was undetectable in normal adult white matter, the site of origin of astrocytomas, while astrocytomas of all grades exhibited significant expression of FGFR-4 mRNA as determined by RT-PCR Southern blot analysis. The proportion of FGFR-4 mRNA did not appear to change in relation to the malignant progression of the astrocytomas. This suggests that induction of FGFR-4 expression in astrocytes represents an early event in their malignant transformation. Induction of FGFR-4 in malignant astrocytomas is consistent with previous reports demonstrating that expression of aFGF, which activates FGFR-4, increases in astrocytomas. The simultaneous induction of FGFR-4 and aFGF may establish a potential autocrine pathway that endows astrocytoma cells with a selective growth advantage. Interestingly, very high expression of FGFR-4 mRNA was found in human fetal brain tissue. The above findings suggest that the malignant transformation of astrocytes may involve the activation of a fetal growth promoting pathway.

Aged↗